Inhibition of emodin on xenografted human K562 cells in nude mice and regulation on relationship of Caspase-3 and Caspase-9 expression.

Objective To explore the inhibitory effects of emodin on xenografted human K562 cells in BALB/c nude mice and its relationship with the expression of Caspase-3 and Caspase-9.Methods The subcutaneously transplanted tumor models of human K562 cells in nude mice were established and then were divided randomly into five groups,including emodin(25,50,and 100 mg/kg),negative control,and hydroxy urine group(120 mg/kg),each of which was composed of five nude mice and then received ip injection in the following 12 d.All mice were sacrificed,tumor volume was measured,and then the weights of tumors were recorded.And the tumor inhibition rate was calculated.Apoptosis morphological transformation of K562 cells induced by emodin was detected by transmission electron microscope and HE staining.RT-PCR was used to detect the expression of caspase-3 and caspase-9 mRNA.Expression of proCaspase-3 and proCaspase-9 protein was determined by Western blotting analysis.Results The relative tumor volume(RTV)was significantly lower in low,moderate,and high dose emodin than that in the negative control group.Compared to negative control group(5.23±0.24,4.38±0.17,and 3.57±0.31 vs 10.45±0.47,P0.01).All the emodin treatment groups showed more obvious inhibition rate(P0.05).Apoptosis and necrosis of tumor cells were found in emodin-treated groups under the light and electron microscope.The results of RT-PCR indicated emodin up-regulated the expression of caspase-3 and caspase-9 mRNA in a dose-dependent manner.Compared with negative control group,the expression of proCaspase-3 and proCaspase-9 protein was down-regulated by emodin at different dosages.ConclusionEmodin could significantly inhibit the growth of K562 cells xenografts in nude mice.The mechanism may be correlated to activate the Caspase-3 and Caspase-9 signaling pathway.